1. Laminin-binding integrins are essential for the maintenance of functional mammary secretory epithelium in lactation.
- Author
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Romagnoli M, Bresson L, Di-Cicco A, Pérez-Lanzón M, Legoix P, Baulande S, de la Grange P, De Arcangelis A, Georges-Labouesse E, Sonnenberg A, Deugnier MA, Glukhova MA, and Faraldo MM
- Subjects
- Animals, Cell Differentiation, Cell Lineage, Cell Proliferation, Cell Survival, Cytoskeleton physiology, Disease Progression, Female, Gene Deletion, Hormones physiology, Integrin alpha3 physiology, Integrin alpha6 physiology, Integrin beta1 physiology, Integrin beta4 physiology, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, Mice, Knockout, Mice, Mutant Strains, Mutation, Neoplastic Stem Cells cytology, Oligonucleotide Array Sequence Analysis, Ovary physiology, Phenotype, Pregnancy, Pregnancy, Animal, Prognosis, Protein Binding, Protein Multimerization, Integrins physiology, Lactation, Mammary Glands, Animal physiology
- Abstract
Integrin dimers α3/β1, α6/β1 and α6/β4 are the mammary epithelial cell receptors for laminins, which are major components of the mammary basement membrane. The roles of specific basement membrane components and their integrin receptors in the regulation of functional gland development have not been analyzed in detail. To investigate the functions of laminin-binding integrins, we obtained mutant mice with mammary luminal cell-specific deficiencies of the α3 and α6 integrin chains generated using the Cre-Lox approach. During pregnancy, mutant mice displayed decreased luminal progenitor activity and retarded lobulo-alveolar development. Mammary glands appeared functional at the onset of lactation in mutant mice; however, myoepithelial cell morphology was markedly altered, suggesting cellular compensation mechanisms involving cytoskeleton reorganization. Notably, lactation was not sustained in mutant females, and the glands underwent precocious involution. Inactivation of the p53 gene rescued the growth defects but did not restore lactogenesis in mutant mice. These results suggest that the p53 pathway is involved in the control of mammary cell proliferation and survival downstream of laminin-binding integrins, and underline an essential role of cell interactions with laminin for lactogenic differentiation., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)
- Published
- 2020
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